Are new technologies in infertility treatment always good news?

Sir,

Your article, “Are new technologies in IVF always good news?” (BMJ 2013; 347: f6004) requires a response in order to provide some balance.

In over 30 years of IVF, assessment of embryo quality has changed little. It is based on morphological assessment at one or two occasions convenient to laboratory management rather than specific embryo stages. Selection of embryos for transfer has remained a subjective process. The principle recent change has seen an increase in the use of extended culture to the blastocyst stage, which RCT evidence has shown to increase implantation rates. However, the consequences of this include increases in the in vitro loss of embryos (confirmed by RCTs) and may include undesirable epigenetic effects upon the embryo and subsequently the baby1. A fundamental tenet of medicine remains, “Do no harm”, and extended culture may breach this coda.

In contrast, time-lapse imaging systems allow embryos to remain in their controlled environment during assessment i.e. they are much less likely to come to harm. However the most important benefit of these systems is that they are leading to the use of objective evaluation of embryo development and selection for transfer at an earlier developmental stage.

There are several time-lapse imaging systems to assess embryo development and, like Simon Fishel, we believe that such technologies are a game changer. We consider that there is strong scientific evidence validating their deployment with immediate effect. The validation includes both demonstration of lower aneuploidy levels in selected embryos and superiority over human assessment in terms of assessing embryo developmental potential2,3.

Whilst we would agree that in an ideal world an RCT is required, the reality is that RCTs only come about once there is a body of observational data to suggest that an innovation may be beneficial. The design of the RCT must be based upon sound observational data. Importantly, none of the currently deployed embryo selection criteria, although supported by learned societies, has been based upon RCT evidence.

It is interesting that the debate cited the precedent of pre-implantation genetic screening (PGS) to determine selection policy for embryo transfer, and how that proved to be a false step. In fact, that case shows that the RCT evidence was inappropriately deployed, because of sub-optimal technology at that time. Newer technologies with comprehensive chromosome screening are showing outstanding results with PGS – with supportive RCT evidence4.

Unfortunately, new technologies are often very expensive, and those involved in patient care must make a judgement call on whether the considerable financial outlay is justifiable – especially in the absence of RCTs. For those of us who work in the private sector, we do not make these decisions lightly as they have implications for the financial health of our business. As such, we have to examine the potential of these technologies and exercise faith in the available scientific data. It is only through these calculated steps, made by private institutions such as the Care Group and ourselves at GCRM, that we will gather enough observational data in order to justify and aid design of RCTs.

The reality is that the NHS relies on the private sector to make these steps, with all their implications, in order to generate sufficient data so that ultimately NHS patients can benefit from these innovations.

Yours,

Dr. Marco Gaudoin, Medical Director
Prof. Richard Fleming, Scientific Director
Mr. Paul Mitchell, Embryologist & Managing Director
GCRM, Glasgow

References
1. Kalra SK, Ratcliffe SJ, Barnhart KT, Coutifaris C. Extended embryo culture and an increased risk of preterm delivery. Obstet Gynecol. 2012;120(1): 69-75.
2. Chavez SL, Loewke KE, Han J, Moussavi F, Colls P, Munne S, Behr B, Reijo Pera RA. Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage. Nat Commun. 2012;3: 1251
3. Conaghan J, Chen AA, Willman SP, Ivani K, Chenette PE, Boostanfar R, Baker VL, Adamson GD, Abusief ME, Gvakharia M, Loewke KE, Shen S. Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial. Fertil Steril. 2013;100(2): 412-9
4. Forman EJ, Hong KH, Franasiak JM, Scott RT Jr. Obstetrical and neonatal outcomes from the BEST Trial: Single embryo transfer with aneuploidy screening improves outcomes after in vitro fertilization without compromising delivery rates. Am J Obstet Gynecol. 2013; (13): 01081-8.